| Project/Area Number |
13671051
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
MOTOKURA Toru FACULTY OF MEDICINE, Lecturer, 医学部附属病院, 講師 (00192823)
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| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | multistep oncogenesis / r-selection / K-selection / p-glycoprotein / multidrug resistance / ARF / p53 |
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| Research Abstract |
By using an SRB assay and a clonogenic assay, we found the emergence of multidrug resistance (MDR) phenotype after K-selection of EJ-ras and c-myc-transformed rat embryo fibroblasts, MR5 and MR8 cells. RT-PCR analysis of expression of drug resistance-related genes suggested the involvement of ABC transporters such as p-glycoprotein/MDR1, MRP1 and BCRP. FACS analysis of doxorubicin intracellular accumulation indicated the augmented P-glycoprotein function in K-selected cells. In order to clarify the molecular mechanisms for refractory disease, we are trying to establish a Burkitt leukemia model for r- and K-selection by using EBV and c-myc oncogene transduction, and also trying to clone target genes which confer tumor cells growth advantages under K-selection by using an retroviral expression cloning system.
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